1. Field of the Invention
This invention relates to a medical composition for injection containing a Spergualin as active ingredient and a process for preparing the same.
2. Description of the Prior Art
Spergualins (I) are useful drugs having cancer control and immunomodulating activities and they have the following structure (see U.S. Pat. Nos. 4,430,346, 4,525,299, and 4,529,549): ##STR5## wherein R is ##STR6## (wherein R' is a lower alkyl group having 1 to 4 carbon atoms,. ##STR7##
Spergualins are labile in aqueous solutions and lose their activity as a result of hydrolysis into the following compounds (II) and (III): ##STR8##
Such substances which are liable in aqueous solutions are conventionally formulated as injections by one of the following two methods: the active ingredient is either dried to a powder form or otherwise solidified by freeze-drying and is converted to an aqueous solution just before use; or the active ingredient is dissolved in non-aqueous solvents such as alcohols and vegetable oils. In the latter method, ethanol, glycerin, propylene glycol and polyethylene glycol 400 are predominantly used as water-miscible non-aqueous solvents, but because of high local toxicity these solvents must be diluted with water before injection. Vegetable oils and other water-immiscible non-aqueous solvents cannot be administered intravenously unless they are emulsified with the aid of surfactants.
Therefore, in order to prepare Spergualin injections that can be administered intraveneously or locally by, for example, intramuscular injection, the first of the two methods shown above is preferred, that is, Spergualin is dried to a powder form or otherwise solidified by freeze-drying and is subsequently converted to an aqueous solution. However, Spergualin is highly hydroscopic and will deliquesce even at a relative humidity of 14% (25.degree. C.). In addition, it is very difficult to obtain Spergualin as crystal.
Therefore, Spergualin alone cannot be easily dried into a powder form or freeze-dried into a solid form having good appearance. Furthermore, a highly hygroscopic drug such as Spergualin defies complete elimination of adsorbed water or may often absorb water during the process of preparing the desired formulation or during transportation or subsequent storage. In the presence of adsorbed water, many excipients will either accelerate the decomposition of the active ingredient or decompose by themselves. For whichever reason, the formulation becomes labile and cannot be used as a stable injection that can be placed on the market.